Since this is a renewal proposal it contains some research work that has been started but not completed, some that is to be extended and new approaches to the problem. The objective of this investigation is unchanged and is aimed at systems analysis for the understanding of neuron destruction and the dynamic behavior of the central nervous system. The limitations of the supply of oxygen and other anabolites to and the removal of carbon dioxide and other metabolites from brain cells influences the efficiency of normal nerve networks. A complete study of the factors which control the rates of supply and removal necessitates the development of adequate mathematical theory. Digital, analog and hybrid computers will be used to solve sophisticated models of anabolite and metabolite transport in the microcirculation of the brain. Steady and unsteady state stochastic models will be developed and solved and compared with experimentally determined oxygen tension histograms and transient responses produced by anoxic - anoxia. Multicomponent deterministic models will be extended to the unsteady state, with superimposed autoregulatory action, to consider the influence of cerebral blood flow changes due to CO2 and O2 levels on tissue oxygenation. Previously proposed controller alogrithms will be tested against experimental results to determine their validity. On-line, real-time feedback control experiments using cats will be performed to determine the practicality of model simulation for clinical applications. Further, on-line testing will be performed to pinpoint the functional relationship between tissue oxygenation level and action potential firing rate. Digital and hybrid Monte Carlo techniques will be upgraded to increase computing speed and refinements in the fluid flow model will be made to determine the relative importance of such refinements.